BACKGROUND Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) and glucose-6-phosphate transporter (SLC37A4), respectively. The high rates of consanguineous marriages in Iran provide a desirable context to facilitate finding the homozygous pathogenic mutations. This study designates to evaluate the clinical and genetic characteristics of patients with GSD1b to assess the possible genotype-phenotype correlation. RESULTS Autozygosity mapping was performed on nineteen GSD suspected families to suggest the causative loci. The mapping was done using two panels of short tandem repeat (STR) markers linked to the corresponding genes. The patients with autozygous haplotype block for the markers flanking the genes were selected for direct sequencing. Six patients showed autozygosity in the candidate markers for SLC37A4. Three causative variants were detected. The recurrent mutation of c.1042_1043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G > A (p.G122E) in the homozygous state were identified in the SLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. A novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Severe and moderate neutropenia was observed in patients with frameshift and missense variants, respectively. The sibling with the whole gene deletion has shown both severe neutropenia and leukopenia. CONCLUSIONS The results showed that the hematological findings may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed.

中文翻译：

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伊朗糖原贮积病 1b (GSD1b) 患者中两种新突变的基因型-表型相关性和描述。

背景技术糖原贮积病(GSD)是一种罕见的先天性糖原代谢合成或降解错误。GSD1是最常见的GSD类型，分为GSD1a和GSD1b，分别由葡萄糖6-磷酸酶（G6PC）和葡萄糖-6-磷酸转运蛋白（SLC37A4）缺乏引起。伊朗近亲结婚的高比率为促进发现纯合致病突变提供了理想的环境。本研究旨在评估 GSD1b 患者的临床和遗传特征，以评估可能的基因型-表型相关性。结果 对 19 个 GSD 疑似家庭进行了自合子作图，以提示致病基因座。使用与相应基因相关的两组短串联重复 (STR) 标记进行映射。选择具有基因侧翼标记的自合单倍型块的患者进行直接测序。六名患者在 SLC37A4 的候选标记中表现出自合子性。检测到三个致病变异。在 SLC37A4 中鉴定了 c.1042_1043delCT (p.Leu348Valfs*53) 的复发突变和纯合状态的 c.365G > A (p.G122E) 的新错义突变。进行计算机分析以预测变体的致病性。还证实了使用远程 PCR 和测序的新型全 SLC37A4 基因缺失。分别在具有移码和错义变异的患者中观察到重度和中度中性粒细胞减少。全基因缺失的兄弟姐妹表现出严重的中性粒细胞减少症和白细胞减少症。结论 结果表明，血液学检查结果可能与基因型检查结果具有适当的相关性。然而，对于明确的基因型-表型相关性，特别是临床和生化表型，需要更大样本量的进一步研究。